LncRNA MALAT1 increases the stemness of gastric cancer cells via enhancing SOX2 mRNA stability

Gastric Cancer is one of the most common malignancies globally; Cancer Stem Cells (CSCs) are regarded as being at the root of tumor progression, and there is thus a need to identify potential drugs to target CSCs. The long non-coding RNA MALAT1 promotes epithelial-mesenchymal transition and angiogenesis in colorectal Cancer, but it is unknown whether it affects the stemness of gastric Cancer cells. Here, we found that knockdown (KD) of MALAT1 attenuated the stemness of non-adherent gastric Cancer cell spheroids, as evidenced by a decrease in primary and secondary spheroid formation capacity and expression of stemness markers. In contrast, overexpression (OE) of MALAT1 enhanced the stemness of adherent gastric Cancer cells. Notably, KD of MALAT1 enhanced radiosensitivity and chemosensitivity of gastric Cancer cell spheroids. We report that MALAT1 directly binds to sox2 mRNA (which encodes a critical master pluripotency factor), enhances the mRNA stability and increases its expression; KD of sox2 partially reversed the effect of MALAT1 OE on the stemness of gastric Cancer cells. Importantly, expression of MALAT1 and sox2 exhibited a positive correlation in clinical samples. Therefore, our results indicate the existence of a novel MALAT1-sox2 axis which promotes the stemness of gastric Cancer cells and may be a potential target for gastric Cancer.